FATE OF AVERMECTIN B-1A IN RATS

Male and female rats were administered [3H]avermectin Blaor a mixture of [3H]- and [14C]avermectin Blaas a single oral dosage at 1.4 or 0.14 mg/kg. Most of the dose (69–82%) was recovered in the feces, with 1% or less found in the urine. The total residue levels in liver, kidney, muscle, and fat tissues were <5.3 ppm at 1 day after dosing and essentially depleted within 7 days after dosing. For all tissues analyzed, the depletion half-life of the total radioactive residue was approximately 1.2 days, while the half-life of avermectin Blawas between 0.6 and 1.0 day. The tissue residue was shown to be qualitatively similar between the tissue type, dose, sex, pretreatment with or without unlabeled avermectin Bla, and label (3H or14C). A major metabolite (32-desmethyl) and a minor metabolite (24-hydroxymethyl) isolated and identified from rat liver microsomal incubations of avermectin Blawere identified in the rat tissues. These two metabolites and avermectin Blaaccounted for >85% of the tissue residue. The fate of [.3H]avermectin Blawas the same as the fate of [14C] avermectin Bla, demonstrating the stability of the3H label on avermectin Blaand the validity of its use in animal metabolism studies. © 1990, American Chemical Society. All rights reserved.